Background: Human papillomavirus infection (HPV infection) is a result of a DNA virus belonging to the Papilloma viridian family, comprising over 170 subtypes, and is widely recognized as the most prevalent sexually transmitted viral infection globally. Prolonged infection with specific HPV strains can lead to the development of cervical cancer. Aim: The study aimed to evaluate the effectiveness of Instructional Guidelines on the early detection of human papillomavirus among high-risk group women, it utilized a Quasi-experimental design. Setting: The study took place at the Early Detection Unit in Ain Shams University Maternity Hospital. A purposive sample of 85 women participated in the study. Tools of data collection: Data was collected using two tools: 1^st Tool; a structured questionnaire sheet that consisted of three parts, socio-demographic characteristics, obstetric history, and assessing knowledge about HPV. 2^nd tool to assess women's attitudes towards HPV. Results: The main findings revealed that before using the instructional guidelines, the participants had low scores in knowledge and attitude towards HPV. However, after implementing the guidelines, there was a significant improvement in both knowledge and attitude scores. The study also found a significant positive correlation between the participants' knowledge levels and their attitudes towards HPV immediately and three months post-intervention (P< 0.0001 & 0.004) respectively. Conclusion: the instructional guideline on HPV was effective in enhancing knowledge and attitudes among the participants. Recommendation: Urgent action is required to implement educational programs for women, delivered by trained healthcare providers, to disseminate information about Human Papilloma Virus and emphasizing the importance of such initiatives.